DESCRIPTION: The investigators' observations to date indicate a central immunomodulatory role for transforming growth factor beta (TGF-beta), a potent immunosuppressive molecule, in human tuberculosis. The sustained support of research at CWRU has delineated mechanisms that may explain the failure of expression of protective immunity during active tuberculosis, and the paradox of skin test anergy in a disease caused by an organism with adjuvant-like properties. M. tuberculosis, its PPD, and its cell wall antigens induce monocytes to production of TGF-beta. TGF-beta is present in tuberculous granulomas and is produced by mononuclear phagocytes of patients with tuberculosis. TGF-beta affects several events in T-cell activation, inhibits the cytokines important in development of a TH 1-like response (IFN-gamma, IL-12), and directly suppresses the TH 1 cytokines (IL-2, IFN-gamma). Further, TGF-beta may promote the expression, or synergize with other suppressive mediators (IL-10), thus amplifying immunosuppressive circuits in situ. A natural inhibitor of TGF-beta, decorin, binds and inactivates TGF-beta and may be clinically useful in diseases such as tuberculosis that are associated with excess TGF-beta activity. Previous observations and the preliminary data support the following hypothesis; the polysaccharide and protein antigens of virulent M. tuberculosis bias the cytokine profile of mononuclear phagocytes towards excess TGF-beta activity. The immunopathogenesis of active tuberculosis involves altered regulation of T-cell activation by TGF-beta which may lead to growth arrest and/or apoptosis of T-cells and an attenuated TH1 response. Down modulation of TGF-beta activity, for example, using the natural inhibitor decorin is expected to enhance such a TH1 response, and, therefore, may be useful as an adjunct to chemotherapy. Specific Aims are: 1. To examine the role of interaction of intact M. tuberculosis through its 30 kD antigen and ManLAM, with fibronectin and mannose receptors on monocytes in expression and activation of TGF-beta. 2. To examine the modulation by TGF-beta of early events in T-cell activation, the growth arrest and/or apoptosis of T-cells stimulated by M. tuberculosis and its products; and the role of TGF-beta in initiating immunosuppressive circuits involving IL-10. 3. To characterize the T-cell dysfunction of patients with active pulmonary tuberculosis, its relationship to TGF-beta and other suppressive cytokines (IL-10) and its reversal by inhibitors of TGF- beta.